Center for Biomolecular Structure Lecture Series

Molecular Events in the Progression of Alzheimer's Disease

Fibrillar aggregates of Abeta peptides and tau protein are defining features of Alzheimer's disease (AD) but the role these structures play in the etiology of disease remains uncertain. Outstanding questions remain as to the distribution of polymorphs between and within cases.  We are using x-ray scanning microdiffraction on histological sections of human brain tissue in order to map the distribution and arrangement of fibrillar aggregates of these proteins in plaques and tangles.  The central hypothesis of the work is that the spatial distribution of structural polymorphs in brain tissue will provide important clues as to how fibrils contribute to disease.  Our goals are to assess whether or not different fibrillar polymorphs spread by a prion-like process during disease progression and to produce data that will provide insight into the structural basis by which different fibrillar strains are associated with different disease subtypes.